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Rho Guanine Nucleotide Exchange FactorsGuanine Nucleotide Exchange FactorsrhoA GTP-Binding Proteinrho GTP-Binding ProteinsGTP-Binding Protein alpha Subunits, G12-G13A Kinase Anchor Proteinsras Guanine Nucleotide Exchange Factorsrho-Associated KinasesSignal TransductionProtein Structure, TertiaryGuanine Nucleotidescdc42 GTP-Binding ProteinProto-Oncogene Proteins c-vavProtein BindingGuanosine Diphosphaterho-Specific Guanine Nucleotide Dissociation InhibitorsGuanine Nucleotide Dissociation InhibitorsMolecular Sequence DataAmino Acid Sequencerac1 GTP-Binding Proteinras-GRF1Guanosine TriphosphateCell Linerho Guanine Nucleotide Dissociation Inhibitor gammarac GTP-Binding ProteinsADP-Ribosylation Factorsrap1 GTP-Binding ProteinsGuanine Nucleotide-Releasing Factor 2rho Guanine Nucleotide Dissociation Inhibitor alphaGTPase-Activating ProteinsSOS1 ProteinGTP-Binding ProteinsADP-Ribosylation Factor 1GTP Phosphohydrolasesral Guanine Nucleotide Exchange FactorSon of Sevenless Proteinsrab GTP-Binding ProteinsEukaryotic Initiation Factor-2Bras ProteinsGuanineral GTP-Binding Proteinsrap GTP-Binding ProteinsSequence Homology, Amino AcidCOS CellsProteinsEnzyme Activationrho Guanine Nucleotide Dissociation Inhibitor betaNucleotidesrab5 GTP-Binding ProteinsMutationAdaptor Proteins, Signal TransducingCoat Protein Complex IRecombinant Fusion ProteinsMonomeric GTP-Binding ProteinsTwo-Hybrid System TechniquesCell Cycle Proteinsp21-Activated KinasesGuanosine 5'-O-(3-Thiotriphosphate)Protein TransportTransfectionActins3T3 CellsPhosphorylationEukaryotic Initiation Factor-2src Homology DomainsProto-Oncogene Proteinsran GTP-Binding ProteinBinding SitesHSP110 Heat-Shock ProteinsProto-Oncogene Proteins p21(ras)Cell MovementHeLa CellsCell MembraneCloning, Molecularrab1 GTP-Binding ProteinsCarrier ProteinsSaccharomyces cerevisiae ProteinsNIH 3T3 CellsBrefeldin ARecombinant ProteinsKineticsSaccharomyces cerevisiaeCytoskeletonModels, BiologicalBase SequenceFungal ProteinsSequence AlignmentOncogene ProteinsStress Fiberscdc42 GTP-Binding Protein, Saccharomyces cerevisiaeGolgi ApparatusMicroscopy, FluorescenceModels, MolecularMembrane Proteinsras GTPase-Activating ProteinsGRB2 Adaptor ProteinCercopithecus aethiopsPhosphoproteinsCells, CulturedrhoB GTP-Binding Protein
GEFsGTPaseProteinsCdc42InhibitorsGTPases RhoMediatesRegulatesInteractionMammalianRhoAPleckstrinBindsIsoformActin cytoskeletonCytoplasmicConformationReceptorCysteine-richRac1TargetsMotifsActivityTrioZinc fingerMorphogenesisDistinctInteractsGeneMembraneVav3RhoGEFTranscriptionProtein familyAminoBindAlpha helicesMolecular
GEFs8
GTPase17
  • FGD1 is a guanine-nucleotide exchange factor (GEF) that can activate the Rho GTPase Cdc42. (wikipedia.org)
  • FGD1 promotes nucleotide exchange on the GTPase Cdc42, a key player in the establishment of cell polarity in all eukaryotic cells. (wikipedia.org)
  • Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl.de)
  • CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket. (embl.de)
  • GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. (embl-heidelberg.de)
  • The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. (embl-heidelberg.de)
  • This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl-heidelberg.de)
  • By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl-heidelberg.de)
  • The structure of the GTPase-activating domain from p50rhoGAP. (embl-heidelberg.de)
  • Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190. (embl-heidelberg.de)
  • The guanine nucleotide exchange factor Sos (Son-of-sevenless) is a complex multidomain protein that activates the small GTPase Ras (H-Ras, K-Ras, N-Ras, but not functionally distinct R-Ras) in response to receptor tyrosine kinase stimulation. (novusbio.com)
  • The distinctive presence of both Rab- and Rho-GTPase GEF activities suggests that C9orf72 may function as a dual exchange factor coupling physiological functions such as cytoskeleton modulation and autophagy with endocytosis. (bath.ac.uk)
  • Mutational analysis revealed that only the C1 and DH domains are essential for Vav3 GEF activity with the C1 region being involved in binding with the GTPase substrate. (cytoskeleton.com)
  • In this study we examined the role of βPix, a guanine nucleotide exchange factor for the Rho GTPase and a strong binding partner to Shank2, in NHE3 regulation using integrated molecular and physiological approaches. (elsevierpure.com)
  • Interestingly, the effects of βPix on NHE3 were abolished by cotransfection with dominant-negative Shank2 mutants and by treatment with Clostridium difficile toxin B, a Rho GTPase inhibitor, indicating that Shank2 and Rho GTPases are involved in βPix-mediated NHE3 regulation. (elsevierpure.com)
  • Growth factor-stimulated mTORC1 activation involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. (abcam.cn)
  • Many, but not all, of these effectors contain a conserved 18 amino-acid binding motif that has been termed CRIB (Cdc42-Rac interactive binding), PBD (p21-binding domain) or GBD (GTPase-binding domain) [ 4 ]. (biomedcentral.com)
Proteins25
  • The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. (antibodies-online.com)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl.de)
  • The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl.de)
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl.de)
  • There are 39736 RhoGEF domains in 38458 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing RhoGEF domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with RhoGEF domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing RhoGEF domain in the selected taxonomic class. (embl.de)
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (embl.de)
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl.de)
  • Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. (embl-heidelberg.de)
  • Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. (embl-heidelberg.de)
  • There are 47093 RhoGAP domains in 46979 proteins in SMART's nrdb database. (embl-heidelberg.de)
  • Taxonomic distribution of proteins containing RhoGAP domain. (embl-heidelberg.de)
  • The complete taxonomic breakdown of all proteins with RhoGAP domain is also avaliable . (embl-heidelberg.de)
  • Rho-specific GAP domains are found in a wide variety of large, multi-functional proteins. (embl-heidelberg.de)
  • Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. (icr.ac.uk)
  • Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. (umbc.edu)
  • This domain occurred 99 times on human genes ( 174 proteins). (umbc.edu)
  • Like the other Vav proteins, Vav3 is phosphorylated (activated) following ligand binding to a variety of receptor tyrosine kinases (TKs), including EGF receptor, PDGF receptor, insulin receptor, and insulin-like growth factor I receptor. (cytoskeleton.com)
  • Scientists discovered before that GTP-hydrolases from the Rho/Rha family proteins are involved in the oncogenic events associated with ovarian cancer. (medicineinnovates.com)
  • These proteins may either trigger the metastatic potential of transformed cells or act as factors that contribute to the transforming activity of oncoproteins. (medicineinnovates.com)
  • FGD1 contains additional motifs commonly associated with signaling proteins, including a pleckstrin homology (PH) domain, an evolutionarily conserved phosphatidylinositol-3-phosphate-binding FYVE domain, and two potential Src-homology 3 (SH3) binding sites. (mhmedical.com)
  • Rho GTPases are small (20-30 kDa) GTP-binding proteins of the Ras superfamily. (biomedcentral.com)
  • This protein belongs to the ROCO (ROC and COR domain) protein family and is made up of five characteristic functional domains: leucine-rich repeats (LRR domain), Rasp of complex proteins (ROC domain), C-terminal of Roc (COR domain), mitogen activated protein kinase kinase kinase (MAPKKK domain), and the WD40 domain. (biomedcentral.com)
Cdc4210
  • The GEF activity of FGD1, which activates Cdc42, is harbored in its DH domain and causes the formation of filopodia, enabling the cells to migrate. (wikipedia.org)
  • The DH domain is required for the activation of Cdc42, through the catalytic exchange of GDP with GTP on Cdc42, while the PH domains confer membrane binding. (wikipedia.org)
  • FGD1 activates Cdc42 by exchanging GDP bound to Cdc42 for GTP and regulates the recruitment of Cdc42 to Golgi membranes. (wikipedia.org)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl.de)
  • The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. (embl.de)
  • Vav3 GTP Exchange Factor (GEF) of Rac1, RhoA and Cdc42. (cytoskeleton.com)
  • From an evolutionary perspective this spatial control is satisfied in that the distant relative S. cerevisiae Cdc24, a GEF for Cdc42, plays a key role in targeting cytoskeletal changes to different spatial domains of the cell in response to different signals O'Shea et al. (justia.com)
  • FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates Cdc42, a member of the Rho (Ras homology) family of the p21 GTPases. (mhmedical.com)
  • The basic signaling properties of two major subgroups of Rho GTPases - the Cdc42 and Rac subfamilies - are highly conserved amongst all eukaryotes, but the means by which they act are not well understood. (biomedcentral.com)
  • The Rho subfamily is divided in three main subgroups - Cdc42, Rac, and Rho - examples of which are represented in all eukaryotes from plants to man. (biomedcentral.com)
Inhibitors1
  • Discovery of a new class of reversible TEA domain transcription factor inhibitors with a novel binding mode. (umassmed.edu)
GTPases Rho1
  • Ory S, Jurdic P. Microtubules, compartiments cellulaires et GTPases Rho: ménage à trois pour une migration efficace. (medecinesciences.org)
Mediates2
  • Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein alpha subunit Galpha13. (umassmed.edu)
  • Bateman J, Shu H, Van Vactor D. The guanine nucleotide exchange factor trio mediates axonal development in the Drosophila embryo. (medecinesciences.org)
Regulates3
  • FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
  • Seipel K, O'Brien SP, Iannotti E, Medley QG, Streuli M. Tara, a novel F-actin binding protein, associates with the Trio guanine nucleotide exchange factor and regulates actin cytoskeletal organization. (medecinesciences.org)
  • These results indicate that βPix up-regulates NHE3 membrane expression and activity by Shank2-mediated protein-protein interaction and by activating Rho GTPases in the apical regions of epithelial cells. (elsevierpure.com)
Interaction5
  • Another interaction partner of FGD1 is cortactin, which is directly bound by the proline-rich domain of FGD1. (wikipedia.org)
  • Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
  • A correlation network between DFS-SEs of splicing factors and non-splicing factors was constructed to determine the potential mechanisms in PRAD, which included the potential regulatory interaction between the splicing event of splicing factor RNA binding motif protein 5-alternate terminator (AT)-64957 and the splicing event of non-splicing factor heterochromatin protein 1 binding protein 3-AT-939. (spandidos-publications.com)
  • The SH3 domain inhibits GEF activity of ARHGEF4 by intramolecular interaction with the DH domain, whereas binding of APC stimulates the GEF activity. (sysmex-flowcytometry.com)
  • LRRK2 encodes a large protein containing three catalytic and four protein-protein interaction domains. (biomedcentral.com)
Mammalian1
  • The Vav family of Rho/Rac guanosine nucleotide exchange factors comprises three members in mammalian cells. (biomedcentral.com)
RhoA2
  • Bellanger JM, Lazaro JB, Diriong S, Fernandez A, Lamb N, Debant A. The two guanine nucleotide exchange factor domains of Trio link the Rac1 and the RhoA pathways in vivo. (medecinesciences.org)
  • The Trio guanine nucleotide exchange factor is a rhoA target : binding of rhoA to the Trio immunoglobulin-like domain. (medecinesciences.org)
Pleckstrin4
  • Signaldependent membrane targeting by pleckstrin homology (PH) domains. (medecinesciences.org)
  • Pleckstrin homology domains interact with filamentous actin. (medecinesciences.org)
  • Besides N-terminal adenomatous polyposis coli (APC)-binding region (ABR) it contains Dbl homology (DH), Pleckstrin homology (PH) and SH3 domains. (sysmex-flowcytometry.com)
  • AFAP1L1 intersects several invadopodia pathway components through its multiple domains and motifs, including the following (i) pleckstrin homology domains that bind phospholipids generated at the plasma membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind Vav2 and Nck2 SH2 domains, respectively. (nature.com)
Binds1
  • The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac- specific and rho-specific guanine nucleotide exchange factor domains. (medecinesciences.org)
Isoform2
  • Vav3, isoform 2) consisting of the three carboxyl terminal domains (SH3, SH2, SH3) differentially expressed in a variety of normal tissues. (cytoskeleton.com)
  • The present invention relates to diagnosing abnormal cell proliferation in biological samples and screening for drugs which inhibit, reduce or abolish cell growth, especially tumorigenic cell growth, by detecting a phosphovariant isoform of a guanine nucleotide exchange factor biomarker, such as the novel GEF-H1S. (justia.com)
Actin cytoskeleton1
Cytoplasmic3
  • In the GTP-bound state, RhoJ interacts with the cytoplasmic domain of PlexinD1. (bvsalud.org)
  • The SH3-SH2-SH3 C-terminal domains bind directly with the auto-phosphorylated cytoplasmic tails of the receptor TKs while the B- and T-cell receptors activate cytosolic TKs. (cytoskeleton.com)
  • ARHGEF4 (Rho guanine nucleotide exchange factor 4), also known as ASEF1 (Adenomatous polyposis coli - stimulated guanine nucleotide exchange factor 1) is an approximately 80 kDa cytoplasmic protein important for growth factor-mediated regulation of cell morphology and migration. (sysmex-flowcytometry.com)
Conformation1
  • The AC's inhibitory conformation is further stabilized through interactions with the CH and DH/PH domains. (cytoskeleton.com)
Receptor3
  • However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (embl.de)
  • Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. (icr.ac.uk)
  • Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR. (research.com)
Cysteine-rich1
  • The DEC-205 monomer forms a compact structure comprising two intercalated rings of C-type lectin-like domains, where the N-terminal cysteine-rich and fibronectin domains reside at the central intersection. (uci.edu)
Rac12
  • Bellanger JM, Astier C, Sardet C, Ohta Y, Stossel TP, Debant A. The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. (medecinesciences.org)
  • This was dependent on Vav-mediated activation of Rac1 as a Dbl domain-mutated Vav, inactive Rac N17, and inactive JNK1 down-regulated the Vav-induced JNK1 or IL-6 responses. (aai.org)
Targets1
  • These findings suggest that distinct Rho GTPases may act as context-dependent integrators of chemotactic cues in directional cell migration and may serve as candidate therapeutic targets to manipulate cell motility in disease or tissue regeneration. (bvsalud.org)
Motifs1
  • The mature human protein contains several characteristic motifs and domains that are involved in the protein's function. (wikipedia.org)
Activity10
  • PH domains are known to specifically bind to polyphosphoinositides and influence the enzymatic activity of the GEF they are located in. (wikipedia.org)
  • Mutations in the FGD1 gene are randomly distributed in all the domains of the protein product, modifying the intracellular localization and/or the GEF catalytic activity of FGD1. (wikipedia.org)
  • Nucleotide exchange activity of Sos is stimulated by allosteric Ras binding. (novusbio.com)
  • By another (separable) guanine exchange factor domain domain Sos modulates activity of Rac/Rho GTPases. (novusbio.com)
  • Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation. (umassmed.edu)
  • The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis. (umassmed.edu)
  • The Rho family of small GTPases and the PDZ (PSD-95/discs large/ZO-1) domain-based adaptor Shank2 are known to regulate the membrane expression and activity of NHE3. (elsevierpure.com)
  • However, the climbing fibre input continuously exerts an activity-dependent repression on parallel fibre synapses, thus confining them to the distal Purkinje cell dendritic domain. (123dok.org)
  • These additional domains may function to regulate the activity and/or location of the FGD1 protein. (mhmedical.com)
  • This study investigates whether the guanine nucleotide exchange activity of Vav is linked to cytokine production in mast cells. (aai.org)
Trio2
  • Trio and its homologue UNC-73 are unique within the Dbl family insomuch as they encode two distinct DH/PH domain modules. (embl.de)
  • The Dab mutant interacts genetically with mutations in Abl , and with mutations in the Abl accessory factors trio and enabled ( ena ). (biologists.com)
Zinc finger1
  • FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF) is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. (wikipedia.org)
Morphogenesis1
Distinct1
  • Using in vitro and cellular techniques, we present a mVP40 assembly model highlighting two distinct oligomerization interfaces: the (N-terminal domain (NTD) and C-terminal domain (CTD)) in mVP40. (uci.edu)
Interacts6
  • The prolin-rich domain interacts with cortactin and actin-binding protein 1. (wikipedia.org)
  • Interacts with NEDD4 (via WW3 domain). (icr.ac.uk)
  • Interacts with SNX9 (via SH3 domain). (icr.ac.uk)
  • Interacts with SRC (via SH2 and SH3 domain). (icr.ac.uk)
  • Interacts (via kinase domain) with AKT1. (icr.ac.uk)
  • Interacts with BCAR1/p130cas via SH3 domains. (icr.ac.uk)
Gene1
  • In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
Membrane1
  • FYVE-finger domains are conserved through evolution and often involved in membrane trafficking (e.g. (wikipedia.org)
Vav31
  • The major isoforms produced from the alternative splicing of Vav3 include full-length Vav3-alpha and N-terminal truncated Vav3.1 (which lack self-regulatory domains). (medicineinnovates.com)
RhoGEF4
  • It is a member of the FYVE, RhoGEF and PH domain containing family. (wikipedia.org)
  • the E-value for the RhoGEF domain shown below is 4.49e-66. (embl.de)
  • It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. (embl.de)
  • the E-value for the RhoGEF domain shown below is 3.6e-56. (embl.de)
Transcription2
  • Specific requirement of Gli transcription factors in Hedgehog-mediated intestinal development. (umassmed.edu)
  • A predictive model of bifunctional transcription factor signaling during embryonic tissue patterning. (umassmed.edu)
Protein family1
Amino1
  • mTORC1 is activated in response to growth factors or amino-acids. (abcam.cn)
Bind1
  • One class of these domains was shown to bind selectively to phosphatidylinositol 3-phosphate. (wikipedia.org)
Alpha helices2
  • The DH domain is composed of 11 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. (embl.de)
  • The domain is composed of seven alpha helices. (embl-heidelberg.de)
Molecular1
  • Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. (novusbio.com)